Patients who respond well to DP-SCIT show immunological differences compared to non-responders. In responders, basal differences include a lower frequency of Th1 and higher frequencies of Th2, Th9 and Th17 cells. After 1 year of treatment, an increased production of sIgG4 was observed in responders, along with a change in Th2 response towards Th1/Treg.

Pru p 3 is the major peach allergen in the Mediterranean area. It frequently elicits severe reactions, limiting its study in humans, raising the need for animal models to investigate the immunological mechanisms involved. However, no anaphylaxis model exists for Pru p 3. We aimed to develop a model of peach anaphylaxis by sensitising mice with Pru p 3 in combination with lipopolysaccharide (LPS) as an adjuvant. Four groups of mice were sensitised intranasally: untreated; treated with Pru p 3; treated with LPS; treated with Pru p 3 + LPS. After sensitisation mice were intraperitoneally challenged with Pru p 3 and in vivo and in vitro parameters were evaluated. Only mice in the Pru p 3 + LPS group showed anaphylaxis symptoms, including a decrease in temperature. Determination of in vitro parameters showed a Th2 response with an increase of Pru p 3-specific IgE and IgG1. Moreover, at the cellular level, we found increased levels of IgE and IgG1 secreting Pru p 3-specific cells and a proliferative CD4+ T-cell response. These results demonstrate that Pru p 3-specific anaphylaxis can be generated after nasal sensitisation to Pru p 3 in combination with LPS. This is a promising model for evaluating food allergy immunotherapies.

Successful Pru p 3-enriched-SLIT is linked to an important immunosuppression of allergen-specific effector T cells, potentially due to an increase of allergen-specific Treg cells. These cellular changes are orchestrated by the activity of moDCs promoting the expression of PD-L1 that will participate in the regulatory response. These changes may serve as biomarkers during SLIT alongside other features such as IgE/IgG ratio.

We report the synthesis and characterisation of gold nanoclusters (Au NCs) stabilised by a mixture of zwitterionic and multivalent mannose ligands. Characterisation of this carbohydrated nanosystem confirms its small size (~2 nm), intense red-NIR fluorescence, relatively high affinity to lectin (ConA), and stability in physiological media. Cell studies performed using human monocyte-derived dendritic cells (DCs) show that Au NC uptake efficiency is greatly enhanced by the presence of surface carbohydrate (> 250% compared to non-carbohydrated Au 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 2 NCs) allowing their detection in cells by fluorescence following incubation with concentrations as low as 1 µg.mL -1 . Investigation using electron microscopy and pharmacological inhibitorsindicates that Au NC uptake is mediated by multiple endocytic pathways involving the engulfment of Au NCs into endosomes and partial transport to lysosomes. Results show that clathrin and F-actin dependent pathways play major roles in Au NC uptake by DCs regardless of whether or not they are coated with carbohydrates. In contrast, a specific C-lectin inhibitor induces a 60% decrease in DC particle uptake only for the carbohydrate-coated Au NCs. This study demonstrates that the combination of ultra-small gold NCs and functionalisation with multivalent mannose ligands results in greatly enhanced human DC targeting, presumably due to increased diffusion and target cell binding, respectively.

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LAR to grass pollen is relevant in patients with seasonal symptoms indicative of allergic rhinitis but with a negative skin test result who live in areas with high allergenic pollen loads. This entity should be included the differential diagnosis of rhinitis.

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Introduction: Mild non-immediate reactions (NIRs) to beta-lactams (BLs) are the most frequent manifestation of drug allergy in children. The diagnostic approach is complex as the utility of skin tests (STs) and lymphocyte transformation tests (LTTs) is controversial. Drug provocation test (DPT) is the gold standard, although no standardized protocols exist. We aimed to investigate the utility of DPT in a unique dose without previous STs, and LTTs in the diagnosis of NIRs to BLs in children. Methods:We prospectively evaluated children 0-14 years old referred to the Regional University Hospital of Málaga during 2017-2020 reporting NIRs to BLs. We performed a DPT with a unique dose followed by regular treatment at home. If positive, STs and LTTs were done after the reaction had disappeared. Results:We included 194 children, having 24 (12.4%) a positive DPT. The main culprit was AX (70.1%) followed by AX-clavulanic acid (CLV) (26.8%) and the main symptoms maculopapular exanthema (MPE) (49.5%) and delayed-urticaria (48.5%). A decrease (p = 0.013) in the interval of days between drug administration and onset of symptoms was observed in positive DPT compared with the original reaction (3.5 vs 6 days), with no differences in the overall percentage of MPE and delayed-appearing urticaria (p = 0.551). No severe reactions occurred during DPT. Moreover, STs were positive in 13.33% and LTTs in 52.9%. Conclusions:Single-dose DPT without previous STs is a safe and useful way to assess NIRs to BLs in children. LTT has shown to be useful, confirming a T-cell mechanism involved in these reactions.